POLYMYXIN B

1. Overview in short 

Polymyxin b is a popular antibacterial that is used to treat a plethora of bacterial infections including bacterial meningitis, sepsis, bronchopneumonia and urinary tract infections. Polymyxins are last resort drugs, usually administered to the patients who fail to respond to first line antibiotics. They have a broad spectrum of activity and are active against a wide range of gram positive as well as gram negative infections. It can be both orally and intravenously administered. One popular example of a polymyxin group of antibiotics is colistin. This report would focus on polymyxin drugs and their use. This report further articulates the importance of this drug on patients undergoing dialysis and patients with CKD (chronic kidney disease). The side effects of the drug will be mentioned, the major drug interactions would be briefed. 

Mode of action: It is a bactericidal drug that leads to the leakage of intracellular components from the bacterial cytoplasmic membrane. This leads to increase of the permeability of the outer cell membrane, eventually leading to bacterial cell death. 

2. Use of polymyxin b specific to kidneys

The retrospective study of (Meiling and Wu in 2018), examined the effect of polymyxin antibiotic on patients with renal impairment’s dose administered was 100 mg daily for 24 days. The results suggested that there was a significant improvement in the renal function before the discharge of the patient from the hospital. Polymyxin B and colistin are antibacterial that are known to exacerbate renal injury and are nephrotoxic and neurotoxic. Polymyxin B is not recommended for patients with renal dysfunction or patients undergoing dialysis. Polymyxin B was a preferred choice over colistin owing to its superior pharmacokinetic property and decreased level of nephrotoxicity. Several studies are suggestive of the fact that polymyxin B clearance is not associated with creatinine clearance. Although the mechanism cannot be comprehended it can be cited as the main clearance pathway for the antibiotic polymyxin B.  

3. Dose in general population IV: 

Systemic infections:

Intravenous dose- The recommended dose of polymyxin B (Rx) should range between 15,000-25,000 units/kg/day divided every 12 hours; and must not exceed not to exceed 25,000 units/kg/day

Intramuscular dose: The recommended dose of polymyxin B (Rx) should range between 25,000-30,000 units/kg per day. 

Intrathecal dose: The recommended dose is 50,000 qDay for 3-4 days; thereafter, negative CSF cultures and normal glucose content, qDay or qODay is recommended for at least 15 days

The total daily dose should not exceed 2,000,000 units per day.

4. Dose especially mention in kidney disease and in dialysis patients

Creatinine clearance is a major parameter of renal insufficiency. When the creatinine clearance or CrCl >20 mL/minute: then 75-100 percent normal dose/day divided q12hr must be provided. When the CrCl is 5-20 mL/minute: then 50 percent usual dose/day divided q12hr must be administered. When the CrCl is 5 mL/minute, then 15 percent usual dose/day q12hr should be given.

5. Side effects especially on kidneys 

Owing to the narrow therapeutic index, polymyxins are extremely nephrotoxic. Polymyxins accumulate in the body and its accumulation leads to programmed cell death or cell apoptosis. This leads to renal dysfunction and causes major histopathological or tissue damage. Several research studies have indicated that increased exposure to polymyxins caused dilation in renal tubules causing tissue scarring and necrosis in a timely manner and dose dependent manner. One of the most adverse side effects of polymyxins B is to cause acute kidney injury (AKI). Such incidences relate to poor prognosis, and leads to higher rate of mortality among patients. Patients with AKI when exposed to polymyxin therapy, experienced greater incidences of Acute kidney injury (AKI). Higher age and weight have been known to increase the risk of developing AKI and the effect has been termed as dose independent. These are potential non modifiable factors. There are several modifiable factors as well for instance the use of nephrotoxic drugs. Calcineurin inhibitors, non-steroidal inflammatory drugs have been identified as the modifiable risk factors. Antibiotics like vancomycin, aminoglycosides and rifampin when co- administered with colistin has been known to increase the incidence of nephrotoxicity in CKD patients. 

6. Only major drug interactions 

Polymyxin can have interactions with other drugs that are harmful for the kidneys. These drugs include cisplatin, aspirin (when present in higher dosage), aminoglycoside antibiotics like amikacin, gentamicin, tobramycin as well as non-steroidal anti-inflammatory drugs like NSAIDs which includes the major pain relievers e.g ibuprofen and naproxen. The important nephrotoxic reactions include albuminuria or presence of albumin protein in the urine, elevated levels of albumin in the blood, without any subsequent increase in the dosage.

7. Brands available in India

DROPS: PHARMACEUTICAL FORMULATION

 OINTMENTS: PHARMACEUTICAL FORMULATION

Conclusion: 

This report has shed light on the antibacterial drug polymyxin B. This drug is usually used for treating multidrug resistant bacterial infections and also in patients with renal insufficiency. This drug tends to cause nephrotoxic effects on the kidney. This is basically a last resort drug. These drugs also interact with other drugs that increase the likelihood of renal damage. As per the current guidelines, polymyxin B is not recommended for patients with renal impairment or patients undergoing dialysis owing to its narrow therapeutic index. In patients with renal impairment, polymyxin can be taken only in small amounts.